ORCID Profile
0000-0002-5420-4100
Current Organisation
Vanderbilt University Medical Center
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Publisher: Springer Science and Business Media LLC
Date: 05-2017
DOI: 10.1038/NATURE22329
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2013
Publisher: Elsevier BV
Date: 2021
Publisher: Massachusetts Medical Society
Date: 22-07-2010
Publisher: Hindawi Limited
Date: 28-01-2011
DOI: 10.1002/HUMU.21401
Publisher: Elsevier BV
Date: 10-2018
Publisher: Elsevier BV
Date: 02-2005
DOI: 10.1111/J.1523-1755.2005.67113.X
Abstract: Goodpasture's disease [antiglomerular basement membrane (GBM) glomerulonephritis] is a classic autoimmune disease and the only organ-specific autoimmune renal disease in which the antigen is well described. The importance of antibodies against the non-collagenous domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1] is well established. However, observational human studies and studies in experimental systems also imply a role for cell-mediated effector injury. Active experimental autoimmune glomerulonephritis (EAG) was induced by immunization with alpha3-alpha5(IV)NC1 heterodimers in B cell intact C57BL/6 mice and B cell (mu chain-deficient) mice. Passive disease was induced by transferring sera from B cell intact and B cell deficient mice with EAG to RAG-1-/- mice (that lack adaptive immunity). Histologic and functional injury was studied. Despite the absence of B cells and immunoglobulin in B-cell-deficient mice, histologic and functional injury developed in mice immunized with alpha3-alpha5(IV)NC1, with T cells and macrophages in glomeruli. Injury occurred to a similar degree to that found in B-cell-intact mice. Transfer of sera from B-cell-intact mice with EAG containing antibodies (but not from B-cell-deficient mice with EAG) to RAG-1-/- mice induced linear immunoglobulin deposits on the glomerular basement membrane (GBM) and pathologic proteinuria. Both cell-mediated and humoral effectors are capable of inducing renal injury in EAG. Given the similarity of the disease-initiating antigen in this model to the antigen in human anti-GBM glomerulonephritis, similar overlapping mechanisms are likely to operate in human disease.
Publisher: Oxford University Press (OUP)
Date: 08-10-2008
DOI: 10.1093/NDT/GFN722
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2004
DOI: 10.1097/01.ASN.0000128968.27705.5E
Abstract: IL-12 and IFN-gamma play key roles in murine lupus and planted antigen models of glomerulonephritis. However, their roles in renal organ-specific autoimmunity are unknown. To establish the roles of endogenous IFN-gamma and IL-12 in experimental autoimmune anti-glomerular basement membrane (GBM) glomerulonephritis (EAG), EAG was induced in normal C57BL/6 mice (WT), IL-12p40-deficient (IL-12p40-/-) mice, and IFN-gamma-deficient (IFN-gamma-/-) mice by immunization with alpha3-alpha5(IV)NC1 heterodimers. At 13 wk, WT mice developed EAG with linear mouse anti-GBM antibody deposition, histologic injury, proteinuria, and mild tubulointerstitial disease. Compared with WT mice, IL-12p40-/- mice had decreased histologic injury and trends to decreased leukocyte infiltrates. In contrast, 40% (4 of 10) of IFN-gamma-/- mice developed significant crescent formation and focal or diffuse interstitial infiltrates (WT, 0 of 8). Compared with WT and/or IL-12p40-/- mice, IFN-gamma-/- mice developed increased injury: histologic injury, total glomerular cell numbers, leukocytes in glomeruli, and renal expression of P-selectin and intercellular adhesion molecule 1. All groups developed similar serum anti-alpha3-alpha5(IV)NC1 antibodies and glomerular Ig deposition, but IFN-gamma-/- mice had decreased anti-alpha3-alpha5(IV)NC1 IgG2a. Therefore, IFN-gamma-/- mice developed increased cellular reactants despite a potentially less damaging antibody response. Dermal delayed-type hypersensitivity was increased in alpha3-alpha5(IV)NC1 immunized IFN-gamma-/- mice and was suppressed by recombinant murine IFN-gamma. CD4+ cells from draining nodes of immunized IFN-gamma-/- mice showed increased proportions of proliferating CD4+ cells but similar numbers of apoptotic cells. These studies demonstrate that in renal organ-specific autoimmunity, IL-12 is pathogenetic but IFN-gamma is protective. They lend weight to the hypothesis that depending on the context/severity of the nephritogenic immune response IFN-gamma has different effects.
Location: United States of America
No related grants have been discovered for Billy Hudson.